Most Americans consume low quantities of long-chain omega-3 (-3) fatty acids, despite clinical evidence that increasing dietary intake of long-chain -3 fatty acids by fish consumption or fish oil supplementation reduces major cardiovascular disease (CVD) events. Moreover, despite clinical evidence of their efficacy, the mechanisms by which long-chain -3 fatty acids protect against CVD events remain uncertain. Because long- chain -3 fatty acids are concentrated in the brain and appear to have efficacy in the treatment of psychiatric disorders that are highly co-morbid with CVD, -3 fatty acid CVD protection may derive, in part, from salutary effects on brain-mediated behavioral risk factors for heart disease. In line with this suggestion, this 2-year ancillary research plan seeks to augment data collection of an ongoing randomized and placebo-controlled trial of -3 fatty acid supplementation, which is a component of our current NHLBI Program Project, "Biobehavioral Studies of Cardiovascular Disease" (HL040962). The aims of this ongoing trial are to test the effects of increasing intake of the key -3 fatty acids - eicosapentaenoic and docosahexaenoic acids (EPA, DHA) - on targets of CVD prevention, including systemic inflammation, cardiac autonomic control, and two brain-mediated behavioral CVD risk factors: negative affect (e.g., depressive symptomatology, hostility, and anger-related traits), and reward-related impulsive decision-making and delay discounting (predisposing to health-impairing habits of lifestyle). To augment our ongoing clinical trial in light of converging neurobiological evidence, we specifically propose to utilize contemporary structural and functional brain imaging techniques to examine the longitudinal effects of -3 fatty acids on brain systems implicated in affect regulation and impulsive decision- making. In this way, the proposed research would determine if increased EPA and DHA consumption reduces (from pre-to-post trial assessments) the reactivity of the amygdala to negative affect-related stimuli, and if increased EPA and DHA consumption the reduces reactivity of the ventral striatum to reward-related stimuli. Finally, the proposed research would explore possible longitudinal effects of increased intake of -3 fatty acids on gray matter morphology in prefrontal, amygdalar, hippocampal, or striatal areas implicated in affective and reward-related behaviors. PUBLIC HEALTH RELEVANCE: Omega-3 fatty acids are essential nutrients for both cardiovascular and behavioral health, and recent trials demonstrate that increasing dietary intake of omega-3 fatty acids protects against cardiovascular disease events. This proposal would augment our ongoing clinical trial in healthy adults by providing for longitudinal assessments of structural and functional brain imaging data, enabling us to determine the potential neural mechanisms for the putative effects of omega-3 fatty acids on two behavioral risk factors for cardiovascular disease - negative affect and impulsive decision-making (as related to health behavior choices).